ARTN_HUMAN
ID ARTN_HUMAN Reviewed; 220 AA.
AC Q5T4W7; D3DPY1; D3DPY3; O95441; O96030; Q6P6A3;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Artemin;
DE AltName: Full=Enovin;
DE AltName: Full=Neublastin;
DE Flags: Precursor;
GN Name=ARTN; Synonyms=EVN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND VARIANT ARG-19.
RX PubMed=9883723; DOI=10.1016/s0896-6273(00)80649-2;
RA Baloh R.H., Tansey M.G., Lampe P.A., Fahrner T.J., Enomoto H.,
RA Simburger K.S., Leitner M.L., Araki T., Johnson E.M. Jr., Milbrandt J.;
RT "Artemin, a novel member of the GDNF ligand family, supports peripheral and
RT central neurons and signals through the GFRalpha3-RET receptor complex.";
RL Neuron 21:1291-1302(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), FUNCTION, TISSUE
RP SPECIFICITY, AND VARIANT ARG-19.
RX PubMed=10583383; DOI=10.1046/j.1432-1327.1999.00925.x;
RA Masure S., Geerts H., Cik M., Hoefnagel E., Van Den Kieboom G.,
RA Tuytelaars A., Harris S., Lesage A.S.J., Leysen J.E., van der Helm L.,
RA Verhasselt P., Yon J., Gordon R.D.;
RT "Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF)
RT family with growth promoting activity on neuronal cells. Existence and
RT tissue-specific expression of different splice variants.";
RL Eur. J. Biochem. 266:892-902(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-19.
RC TISSUE=Brain;
RX PubMed=10673327; DOI=10.1006/mcne.1999.0817;
RA Rosenblad C., Gronborg M., Hansen C., Blom N., Meyer M., Johansen J.,
RA Dago L., Kirik D., Patel U.A., Lundberg C., Trono D., Bjoerklund A.,
RA Johansen T.E.;
RT "In vivo protection of nigral dopamine neurons by lentiviral gene transfer
RT of the novel GDNF-family member neublastin/artemin.";
RL Mol. Cell. Neurosci. 15:199-214(2000).
RN [4]
RP ERRATUM OF PUBMED:10673327.
RA Rosenblad C., Gronborg M., Hansen C., Blom N., Meyer M., Johansen J.,
RA Dago L., Kirik D., Patel U.A., Lundberg C., Trono D., Bjoerklund A.,
RA Johansen T.E.;
RL Mol. Cell. Neurosci. 18:332-333(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 122-220 IN COMPLEX WITH GFRA3,
RP DISULFIDE BONDS, AND SUBUNIT.
RX PubMed=16765900; DOI=10.1016/j.str.2006.05.010;
RA Wang X., Baloh R.H., Milbrandt J., Garcia K.C.;
RT "Structure of artemin complexed with its receptor GFRalpha3: convergent
RT recognition of glial cell line-derived neurotrophic factors.";
RL Structure 14:1083-1092(2006).
CC -!- FUNCTION: Ligand for the GFR-alpha-3-RET receptor complex but can also
CC activate the GFR-alpha-1-RET receptor complex. Supports the survival of
CC sensory and sympathetic peripheral neurons in culture and also supports
CC the survival of dopaminergic neurons of the ventral mid-brain. Strong
CC attractant of gut hematopoietic cells thus promoting the formation
CC Peyer's patch-like structures, a major component of the gut-associated
CC lymphoid tissue. {ECO:0000269|PubMed:10583383,
CC ECO:0000269|PubMed:9883723}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Binds to RET (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q5T4W7; O60609: GFRA3; NbExp=4; IntAct=EBI-15586241, EBI-15586309;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5T4W7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5T4W7-2; Sequence=VSP_019335;
CC Name=3;
CC IsoId=Q5T4W7-3; Sequence=VSP_019336;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed at high levels in peripheral
CC tissues including prostate, placenta, pancreas, heart, kidney,
CC pituitary gland, lung and testis. Expressed at low levels in the brain.
CC {ECO:0000269|PubMed:10583383, ECO:0000269|PubMed:9883723}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis. High level
CC expression seen in fetal kidney and lung while a low level expression
CC seen in the fetal brain. {ECO:0000269|PubMed:9883723}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. GDNF subfamily.
CC {ECO:0000305}.
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DR EMBL; AF109401; AAC98690.1; -; mRNA.
DR EMBL; AF115765; AAD13109.1; -; Genomic_DNA.
DR EMBL; AF115765; AAD13110.1; -; Genomic_DNA.
DR EMBL; AJ245628; CAB52396.1; -; Genomic_DNA.
DR EMBL; AF120274; AAD21075.1; -; mRNA.
DR EMBL; AL357079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07074.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07077.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07079.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07078.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07080.1; -; Genomic_DNA.
DR EMBL; BC062375; AAH62375.1; -; mRNA.
DR CCDS; CCDS501.1; -. [Q5T4W7-1]
DR CCDS; CCDS502.1; -. [Q5T4W7-3]
DR RefSeq; NP_001129687.1; NM_001136215.1. [Q5T4W7-3]
DR RefSeq; NP_476431.2; NM_057090.2. [Q5T4W7-3]
DR RefSeq; NP_476432.2; NM_057091.2. [Q5T4W7-1]
DR PDB; 2ASK; X-ray; 1.55 A; A/B=108-220.
DR PDB; 2GH0; X-ray; 1.92 A; C/D=122-220.
DR PDB; 2GYR; X-ray; 2.60 A; A/B/C/D/E/F=122-220.
DR PDB; 2GYZ; X-ray; 1.76 A; A=122-220.
DR PDB; 6Q2S; EM; 3.80 A; A/B=108-220.
DR PDBsum; 2ASK; -.
DR PDBsum; 2GH0; -.
DR PDBsum; 2GYR; -.
DR PDBsum; 2GYZ; -.
DR PDBsum; 6Q2S; -.
DR AlphaFoldDB; Q5T4W7; -.
DR SMR; Q5T4W7; -.
DR BioGRID; 114510; 1.
DR CORUM; Q5T4W7; -.
DR DIP; DIP-29113N; -.
DR IntAct; Q5T4W7; 1.
DR STRING; 9606.ENSP00000387435; -.
DR GlyGen; Q5T4W7; 1 site.
DR iPTMnet; Q5T4W7; -.
DR PhosphoSitePlus; Q5T4W7; -.
DR BioMuta; ARTN; -.
DR DMDM; 74744994; -.
DR PaxDb; Q5T4W7; -.
DR PeptideAtlas; Q5T4W7; -.
DR PRIDE; Q5T4W7; -.
DR TopDownProteomics; Q5T4W7-3; -. [Q5T4W7-3]
DR ABCD; Q5T4W7; 6 sequenced antibodies.
DR Antibodypedia; 18382; 365 antibodies from 31 providers.
DR DNASU; 9048; -.
DR Ensembl; ENST00000372354.3; ENSP00000361429.3; ENSG00000117407.17. [Q5T4W7-1]
DR Ensembl; ENST00000372359.10; ENSP00000361434.5; ENSG00000117407.17. [Q5T4W7-1]
DR Ensembl; ENST00000414809.7; ENSP00000387435.3; ENSG00000117407.17. [Q5T4W7-3]
DR Ensembl; ENST00000438616.3; ENSP00000391998.3; ENSG00000117407.17. [Q5T4W7-2]
DR Ensembl; ENST00000498139.6; ENSP00000436727.1; ENSG00000117407.17. [Q5T4W7-3]
DR GeneID; 9048; -.
DR KEGG; hsa:9048; -.
DR MANE-Select; ENST00000372359.10; ENSP00000361434.5; NM_057091.3; NP_476432.2.
DR UCSC; uc001cks.4; human. [Q5T4W7-1]
DR CTD; 9048; -.
DR DisGeNET; 9048; -.
DR GeneCards; ARTN; -.
DR HGNC; HGNC:727; ARTN.
DR HPA; ENSG00000117407; Low tissue specificity.
DR MIM; 603886; gene.
DR neXtProt; NX_Q5T4W7; -.
DR OpenTargets; ENSG00000117407; -.
DR PharmGKB; PA25017; -.
DR VEuPathDB; HostDB:ENSG00000117407; -.
DR eggNOG; ENOG502S53F; Eukaryota.
DR GeneTree; ENSGT00950000182993; -.
DR HOGENOM; CLU_102221_0_0_1; -.
DR InParanoid; Q5T4W7; -.
DR OMA; VTQPCCR; -.
DR OrthoDB; 1373819at2759; -.
DR PhylomeDB; Q5T4W7; -.
DR TreeFam; TF332366; -.
DR PathwayCommons; Q5T4W7; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q5T4W7; -.
DR SIGNOR; Q5T4W7; -.
DR BioGRID-ORCS; 9048; 10 hits in 1061 CRISPR screens.
DR EvolutionaryTrace; Q5T4W7; -.
DR GeneWiki; Artemin; -.
DR GenomeRNAi; 9048; -.
DR Pharos; Q5T4W7; Tbio.
DR PRO; PR:Q5T4W7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5T4W7; protein.
DR Bgee; ENSG00000117407; Expressed in triceps brachii and 124 other tissues.
DR ExpressionAtlas; Q5T4W7; baseline and differential.
DR Genevisible; Q5T4W7; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030116; F:glial cell-derived neurotrophic factor receptor binding; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:InterPro.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0050930; P:induction of positive chemotaxis; IEA:Ensembl.
DR GO; GO:0097021; P:lymphocyte migration into lymphoid organs; IEA:Ensembl.
DR GO; GO:0007405; P:neuroblast proliferation; TAS:ProtInc.
DR GO; GO:0007422; P:peripheral nervous system development; IBA:GO_Central.
DR GO; GO:0061146; P:Peyer's patch morphogenesis; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR DisProt; DP02428; -.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR043401; GDNF_fam.
DR InterPro; IPR001839; TGF-b_C.
DR PANTHER; PTHR12173; PTHR12173; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disulfide bond; Glycoprotein;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT PROPEP 40..107
FT /evidence="ECO:0000255"
FT /id="PRO_0000240286"
FT CHAIN 108..220
FT /note="Artemin"
FT /id="PRO_0000240287"
FT REGION 41..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..99
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 123..188
FT /evidence="ECO:0000269|PubMed:16765900"
FT DISULFID 150..216
FT /evidence="ECO:0000269|PubMed:16765900"
FT DISULFID 154..218
FT /evidence="ECO:0000269|PubMed:16765900"
FT DISULFID 187
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:16765900"
FT VAR_SEQ 1..19
FT /note="MELGLGGLSTLSHCPWPRQ -> MPGLISARGQPLLEVLPPQAHLGALFLPE
FT APLGLSA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9883723"
FT /id="VSP_019335"
FT VAR_SEQ 21
FT /note="P -> APLGLSAQP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019336"
FT VARIANT 19
FT /note="Q -> R (in dbSNP:rs2242637)"
FT /evidence="ECO:0000269|PubMed:10583383,
FT ECO:0000269|PubMed:10673327, ECO:0000269|PubMed:9883723"
FT /id="VAR_026718"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:2ASK"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:2ASK"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2ASK"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:2ASK"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:2ASK"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:2ASK"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:2ASK"
FT STRAND 187..199
FT /evidence="ECO:0007829|PDB:2ASK"
FT STRAND 205..219
FT /evidence="ECO:0007829|PDB:2ASK"
SQ SEQUENCE 220 AA; 22878 MW; C61B65EF3A51FEE4 CRC64;
MELGLGGLST LSHCPWPRQQ PALWPTLAAL ALLSSVAEAS LGSAPRSPAP REGPPPVLAS
PAGHLPGGRT ARWCSGRARR PPPQPSRPAP PPPAPPSALP RGGRAARAGG PGSRARAAGA
RGCRLRSQLV PVRALGLGHR SDELVRFRFC SGSCRRARSP HDLSLASLLG AGALRPPPGS
RPVSQPCCRP TRYEAVSFMD VNSTWRTVDR LSATACGCLG
